The general idea for this protocol is based on a novel mechanism for the selective production of Nitric oxide from nitrite, using human hemoglobin as nitrate reductase. This reaction is favored in tissues with low oxygen tension and low pH, such as the environment most likely to occur at leg ulcer sites. This is an open label, Phase I study of topical sodium nitrite for subjects with leg ulcers, of more than 4 weeks duration, who have sickle cell disease or other hemolytic disorders. Twelve subjects with homozygous sickle cell disease (HbSS), sickle-thalassemia (Hb S- thalassemia) or HbSC, HBSD or other hemoglobinopathies or hemolytic disorders will be enrolled at the NIH Clinical Center. Four cohorts of subjects, with three subjects at each dose level, will be treated with escalating doses of topical sodium nitrite cream twice a week based on the modified Fibonacci schema. For dose levels 1 - 4, subjects will have 0.1 cm of sodium nitrite cream applied per 1 square cm of the ulcer. Each area will be rounded to the nearest 1 square cm. The total amount of sodium nitrite administered to each subject will vary depending upon the size of the ulcer but the total surface area will not exceed 100 square cm (i.e. subjects will receive a maximum of 10 cm of sodium nitrite cream). All subjects will receive topical application of the drug twice a week for four weeks total. Three subjects will be treated at each dose level. When none of the subjects experience dose-limiting toxicity (DLT) the next cohort of three subjects will be treated at the next higher dose. If one of three subjects in a cohort experiences DLT then the next cohort will begin at the same dose as the previous cohort. Control group. Based on the literature and our clinical experience, half of the patients with leg ulcers have more than one lesion. If a subject has two or four ulcers, half of the ulcers will be treated with the study cream (nitrite) and the other half with standard of care (randomized by coin flip). If a subject has three ulcers, two will be treated with study cream and one with standard of care. Screening: The subjects will be evaluated at the Clinical Center to determine eligibility, obtain informed consent, detailed medical history and physical examination. A plain x-ray of the leg(s) involved will be performed to rule out underlying osteomyelitis, which represents an exclusion criterion. Doppler ultrasound of the leg(s) will be performed to assess the presence of venous insufficiency and/or thrombosis. Potential subjects will have a detailed wound assessment performed by the wound ostomy continence nurse service (WOCN) to include a wound culture. A seven-day pain inventory tool and a quality of life assessment will be completed prior to initiating therapy. Routine laboratory studies will be obtained along with additional research laboratory tests at baseline and at specified times during the study. The subjects will then be scheduled for a 4-5-day inpatient hospitalization, in order to allow for extensive additional studies, and pharmachokinetics of nitric oxide, sodium nitrite and methemoglobin. The hospitalization will facilitate close monitoring for safety of administration of sodium nitrite cream and the occurrence of side effects. While in the hospital, all subjects will have the following baseline tests: laboratory assessments, measurement of the ulcers size, and a non-contrast MRI. Subjects will then undergo infrared photography in order to measure the perimeter of the ulcers and to identify surface blood vessels that will guide the placement of wireless thermo-patches. Infrared and laser perfusion imaging will be repeated throughout the study at defined time points, as detailed in the protocol. In order to assess histopathological changes in the skin of individuals who have sickle cell disease or other hemolytic disorders, one punch biopsy will be performed in consenting subjects who have more than one leg ulcer and it is on the opposite leg as an optional part of their evaluation. If a subject declines participation in the biopsy portion of the study, he/she will not be excluded from participation in the other portions of the study. After the initial week of inpatient stay, the subjects will be treated as outpatients, and sodium nitrite cream will be applied to the leg ulcer selected for treatment twice a week in the day hospital. Measurements of all the ulcers will be performed at defined time points. The primary expected toxicity during this portion of the study, is low grade, asymptomatic methemoglobinemia, therefore, blood will be drawn at each visit. At the completion of the 4 weeks of therapy, baseline studies will be repeated on an outpatient basis. To date we have enrolled 12 subjects in this study. 6 have completed the study, 2 subjects are currently in the outpatient portion of the study, and the other 4 subjects were not eligible due to wound size or concurrent infection. No subject has suffered serious complications from the application of the cream and we have not observed dose-limiting methemoglobinemia. The cream seems to be well tolerated at each of the strengths used so far. Few subjects experienced a reduction of the ulcer size, and an improvement of the wound characteristics, but the evaluation of response to therapy was a secondary goal and will be assessed when all subjects have completed the study.